ASCO 2026 preview – Celcuity gets a mutant coup

Celcuity is awaiting an FDA decision on its PI3K/mTOR inhibitor gedatolisib in PIK3CA wild-type breast cancer, and it has now bagged a win in PIK3CA-mutant disease – as well as an ASCO late-breaker slot.

After hours on Friday, the group toplined a win in the PIK3CA-mutant portion of the Viktoria-1 trial, saying both a gedatolisib triplet and doublet produced a progression-free survival benefit over control. Full results are being reserved for the conference, where gedatolisib appears to be a new addition to the roster.

Viktoria-1 is evaluating gedatolisib plus Faslodex, with or without Pfizer’s Ibrance, in ER-positive, HER2-negative breast cancer patients who’ve progressed on a CDK4/6 inhibitor and aromatase inhibitor combination.

In the PIK3CA-mutant population, the control arm is Novartis's Piqray plus Faslodex.

All Celcuity is saying is that both the gedatolisib triplet and doublet produced “a statistically significant and clinically meaningful improvement in PFS” versus control. The triplet was used in the primary efficacy analysis, while the doublet was tested secondarily.

A benchmark could come from a phase 1 study, presented at ESMO last year, which found a 14.6 month median PFS with gedatolisib/Faslodex/Ibrance in PIK3CA mutants – rising to an even more impressive 19.7 months with an intermittent gedatolisib dose that’s being used in Viktoria-1.

Historically, Piqray/Faslodex scored mPFS of 11.0 months in the Solar-1 trial, and 7.3 months in Bylieve, which tested a post-CDK4/6 population more analogous to Viktoria-1.

Gedatolisib’s numbers are likely to wane given the usual attrition between phase 1 and 3, but anything approaching this result would be emphatic.

PIK3CA wild types

The gedatolisib doublet and triplet have already impressed in Viktoria-1’s PIK3CA wild-type cohort, and Celcuity is awaiting an FDA approval verdict by 17 July.

One reason for caution could be a 69% rate of stomatitis (19% at grade 3+), which is higher than seen with Piqray, Itovebi or Truqap. 

However, Celcuity looks likely to be heading towards its first approved drug, which is particularly notable given it acquired the asset from Pfizer for just $5m in cash plus $5m in equity in 2021.

As for the competition, Piqray is only approved for PIK3CA-mutant breast cancer; while gedatolisib’s potential in PIK3CA wild-type disease is a differentiating factor, a PIK3CA-mutant win was seen as key to a broad label.

Celcuity’s stock closed up 15% on Monday, giving the group a market cap of $7bn.

Viktoria-1 trial of gedatolisib in second-line ER+ve, HER2-ve breast cancer

Source: OncologyPipeline.